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El estudio muestra los cambios en aspectos epistemológicos, conceptuales, didácticos y estructurales, de cinco maestros de primaria antes y después de participar en un proceso de discusión crítica de sus prácticas de enseñanza en la argumentación en la clase de ciencias. Con el fin de identificar los cambios en los cuatro aspectos, a la información obtenida tras la aplicación de un cuestionario inicial y final, se le realizó un análisis de contenido. Los resultados mostraron un cambio significativo en los componentes: epistemológico, conceptual y didáctico y no tanto en el estructural. Con estos resultados, se ratificó la importancia de ofrecer espacios de participación a los maestros para discutir, evaluar y proponer mecanismos de mejora de sus prácticas en el aula.

Este artículo aborda el problema de la participación de los pobladores en Chile a través del análisis de dos casos paradigmáticos de las políticas sociales de vivienda: Villa La Reina, construida en 1967, durante la llamada Revolución en Libertad y Villa San Arturo, construida treinta años después, durante el período de la Concertación democrática. A través del análisis de estos dos períodos podremos observar como el diseño de políticas de viviendas para los más pobres y excluidos de nuestra sociedad, han perdido fuerza en ciertos principios básicos a los procesos de construcción de una sociedad más democrática, igualitaria e integradora.

Microelectronic computers have encountered challenges in meeting all of today’s demands for information processing. Meeting these demands will require the development of unconventional computers employing alternative processing models and new device physics. Neural network models have come to dominate modern machine learning algorithms, and specialized electronic hardware has been developed to implement them more efficiently. A silicon photonic integration industry promises to bring manufacturing ecosystems normally reserved for microelectronics to photonics. Photonic devices have already found simple analog signal processing niches where electronics cannot provide sufficient bandwidth and reconfigurability. In order to solve more complex information processing problems, they will have to adopt a processing model that generalizes and scales. Neuromorphic photonics aims to map physical models of optoelectronic systems to abstract models of neural networks. It represents a new opportunity for machine information processing on sub-nanosecond timescales, with application to mathematical programming, intelligent radio frequency signal processing, and real-time control. The strategy of neuromorphic engineering is to externalize the risk of developing computational theory alongside hardware. The strategy of remaining compatible with silicon photonics externalizes the risk of platform development. In this perspective article, we provide a rationale for a neuromorphic photonics processor, envisioning its architecture and a compiler. We also discuss how it can be interfaced with a general purpose computer, i.e. a CPU, as a coprocessor to target specific applications. This paper is intended for a wide audience and provides a roadmap for expanding research in the direction of transforming neuromorphic photonics into a viable and useful candidate for accelerating neuromorphic computing.

Objective. To evaluate the association of -174G/C IL-6 polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for IL-6 -174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2). Results. Patients with MTX or LEF had significant decrement in DAS-28 (p<0.001); nevertheless, only 14% and 12.5% achieved DAS-28 < 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07–1.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05–2.3; p=0.003), or CC (RR = 1.83; 95% CI = 1.07–3.14; p=0.001). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03–1.72; p=0.02). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded that IL-6 -174G/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF. [ABSTRACT FROM AUTHOR]

Background: We describe a family with a 7-year-old proband case diagnosed with systemic lupus erythematosus (SLE) plus secondary anti-phospholipid syndrome (APS) as well as two affected paternal aunts. We compared the frequency of these polymorphisms with healthy controls. Objectives: To evaluate the mode of inheritance in this familial case of APS and SLE and the possible association of plasminogen activator inhibitor-1 (PAI-1) -675 4G/5G and PAI-2 Ser413/Cys polymorphisms. To compare the genotype frequency of these polymorphisms with the results found in a Mexican Mestizo population. Methods: PAI-1 -675 4G/5G and PAI-2 Ser413/Cys were determined by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique using Bsl I and Mwo I on four generations of the family studied. PAI-2 Ser413/Cys polymorphism was also determined in 50 healthy individuals of Mexican Mestizo origin. Results: The family pedigree demonstrated that this family did not follow a Mendelian inheritance pattern. When the PAI-2 Ser413/Cys polymorphism was examined, we found that 60% (3/5) of the relatives homozygous to Ser413/Ser were affected with SLE and/or APS (p = 0.027). The proband case was 4G/5G genotype for the PAI-1 -675 4G/5G polymorphism. No differences between healthy controls of the Mexican Mestizo population and the family studied for the PAI-2 Ser413/Cys polymorphism or PAI-1 -675 4G/5G polymorphisms were found. Conclusions: Our data indicate that this family did not follow the Mendelian inheritance pattern. The Ser413/Ser genotype demonstrated in 60% of the affected members (3/5) of this family might increase the risk for autoimmune syndromes such as APS or SLE. [ABSTRACT FROM AUTHOR]

A new species of the freshwater planktonic copepod genus Leptodiaptomus is described for a small pond in Northwestern Mexico. Leptodiaptomus dodsoni n. sp. can be easily distinguished mainly by the presence of an unusually large sinusoid spine on male antennular segment 13, and by the features of the fifth legs of both sexes. This genus is known to be distributed mainly in North America with 19 recognized species. Of these, six ocur in Mexico, and the new species seems to be closely related to most of them. It is probable that this group of species (including the new one) represents the southwards radiation of the genus from North America. Compared to the Caribbean and South American, the North American influence seems to be the most relevant for diaptomid copepods in Mexico. At least two Mexican species of Leptodiaptomus, including L.dodsoni, are restricted in distributional range to high-altitude temporal ponds, and both could be considered endemics. [ABSTRACT FROM PUBLISHER]

Introduction: Villaverde's day hospital is an intensive psychotherapeutic treatment Center for adult patients (from 18 to 65 years old) with severe mental disorder. Our patients are included in different group therapies with a therapeutic community approach and a multidisciplinary view, with occupational therapy being an important part of their treatment. Working with patients through occupational therapy (OT) may change depending on the kind of patients treated and the type of units they are on. Objectives: Our OT team has observed a change on the point of view of our patients regarding OT compared to previous experiences so we want to analyze this change in their perspective. Methods: We performed individual interviews focusing on their experience with OT, enquiring about what motivated this change. Results: Through their testimonies, our patients describe a better experience with occupational therapy in our day hospital compared to other units they have been treated on. Conclusions: We believe this change is due to different aspects. Usually our patients come into contact with occupational therapy in acute units, where the main focus is on occupational tasks. In our hospital, occupational therapy has its focus on the patients problems or biography, which they approach through a creative perspective. [ABSTRACT FROM AUTHOR]

The article focuses on a study regarding the expression of the T helper (Th)1/Th2 cytokine profile and the NF-κB activity on women with autoimmune rheumatic diseases particularly in pregnancy. Pregnant women with systemic lupus erythematosus (SLE) usually developed exacerbations. The study suggests that the success or the failure of the development of pregnancy or related to the underlying diseased cannot be explained only by cytokine profile expressed.

Abstract: The consumption of drinking water rich in fluoride has toxic effects on the central nervous system. In cell biology research, fluoride is currently used as a phosphatase inhibitor. The aim of the present study was to evaluate the effect of fluoride on different physiological processes in GH4C1 pituitary tumour cells. We used a range of different fluoride concentrations, from levels below normal human serum concentrations (0.23 and 1.2μmol/L) to those observed in chronically exposed persons (10.7μmol/L) and above (107 and 1072μmol/L). Treatment of 10.7μmol/L fluoride resulted in a discrete induction of DNA synthesis, without a change in cell number. Cell migration, a behaviour stimulated by growth factors, was increased in cells treated with 2.4μmol/L. At this fluoride concentration, changes in phosphorylation status of both cytoskeletal and cytosolic protein fractions, as well as in actin cytoskeletal arrangements were observed. The GH4C1 fluoride treated cells had significantly less cellular protein than control cells, suggesting an effect of fluoride on hormone secretion and protein synthesis in this endocrine cell. The bioreduction of MTT was significantly increased with a wide range of fluoride concentrations. With the highest fluoride concentration, 1072μmol/L, all of the analysed parameters were significantly reduced, suggesting that this dose is highly toxic in GH4C1 cells. Our results show that biologically relevant concentrations of fluoride are capable of increasing cell migration in tumour cells, suggesting that exposure to fluoride could stimulate tumour invasion. [Copyright &y& Elsevier]

Rheumatoid arthritis (RA) is a chronic and inflammatory disease with prominent manifestation in diarthrodial joints, where the plasminogen activator system is believed to be involved in proteolytic degradation. Plasmin play a pivotal role in the degradative process of cartilage through the activation of latent metalloproteases. Objective: To investigate 4G/5G PAI-1 polymorphism in patients with RA, OA (osteoarthritis) and healthy subjects and its association with lipid profile. Patient and Methods: We recruited 33 RA, 31 OA patients and 30 healthy subjects. PAI-1 genotype was done by PCRRFLP's. Statistical analysis was performed using SPSS 10.0 and Epi Info. Results: Genotype 5G/5G, 4G/5G, 4G/4G frequency in patients with RA was: 0.45, 0.52, 0.03; whereas in OA was: 0.32, 0.55, 0.13, and in healthy subjects was 0.23, 0.6 and 0.16 respectively. In addition, with respect to 5G allelic frequency, a significant difference between RA and healthy subjects (0.71 vs 0.53, p<0.05; OR 2.16; 95%, IC 0.97-4.84) was observed. With regard to the lipid profile, healthy subjects with 5G/5G genotype presented increased levels of triglycerides (195.43±86.87) and VLDL-c (39.08±17.37) in comparison with 4G/5G and 4G/4G genotypes (p<0.05). Conclusions: Mexican population is in Hardy-Weinberg equilibrium. This data support the possibility that the 5G allele of the PAI-1 gene may be a surrogate marker for RA; whereas the 4G allele may be a protective factor to develop this disease. 5G/5G genotype is associated with high levels of triglycerides and VLDL-c in healthy subjects, which suggests that the levels of these parameters are related with the genotype. [ABSTRACT FROM AUTHOR]

Abstract: Metabolic indices of neuronal activity are thought to predict changes in the frequency of action potentials. There are stimuli that do not shift action potential frequency but change the temporal organization of neuronal firing following modifications of excitatory inputs by inhibitory synaptic activation. To our knowledge it is unknown whether this kind of stimulus associates with adjustments of metabolic markers of neuronal activity. Here, we used the hypothalamic–neurohypophysial system of lactating rats to address whether shifts in the temporal organization of neuronal firing relate with modifications of metabolic markers of neuronal activity. Cytochrome oxidase activity, 3H-2-deoxyglucose uptake, and the area occupied by blood vessels increased in the paraventricular nucleus and neurohypophysis of lactating rats, as compared with their virgin counterparts. Taken together, these results suggest that metabolic demands denote shifts in the temporal organization of action potentials related with the adjustment of excitatory synaptic activation, and support that changes in metabolic markers do not necessarily reflect shifts in the frequency of action potentials. [Copyright &y& Elsevier]

The global surge in energy demand, driven by technological advances and population growth, underscores the critical need for effective management of electricity supply and demand. In certain developing nations, a significant challenge arises because the energy demand of their population exceeds their capacity to generate, as is the case in Iraq. This study focuses on energy forecasting in Iraq, using a previously unstudied dataset from 2019 to 2021, sourced from the Iraqi Ministry of Electricity. The study employs a diverse set of advanced forecasting models, including Linear Regression, XGBoost, Random Forest, Long Short-Term Memory, Temporal Convolutional Networks, and Multi-Layer Perceptron, evaluating their performance across four distinct forecast horizons (24, 48, 72, and 168 hours ahead). Key findings reveal that Linear Regression is a consistent top performer in demand forecasting, while XGBoost excels in supply forecasting. Statistical analysis detects differences in models performances for both datasets, although no significant differences are found in pairwise comparisons for the supply dataset. This study emphasizes the importance of accurate energy forecasting for energy security, resource allocation, and policy-making in Iraq. It provides tools for decision-makers to address energy challenges, mitigate power shortages, and stimulate economic growth. It also encourages innovative forecasting methods, the use of external variables like weather and economic data, and region-specific models tailored to Iraq's energy landscape. The research contributes valuable insights into the dynamics of electricity supply and demand in Iraq and offers performance evaluations for better energy planning and management, ultimately promoting sustainable development and improving the quality of life for the Iraqi population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

This work examines the possible behaviour of Neanderthal groups at the Cueva Des-Cubierta (central Spain) via the analysis of the latter's archaeological assemblage. Alongside evidence of Mousterian lithic industry, Level 3 of the cave infill was found to contain an assemblage of mammalian bone remains dominated by the crania of large ungulates, some associated with small hearths. The scarcity of post-cranial elements, teeth, mandibles and maxillae, along with evidence of anthropogenic modification of the crania (cut and percussion marks), indicates that the carcasses of the corresponding animals were initially processed outside the cave, and the crania were later brought inside. A second round of processing then took place, possibly related to the removal of the brain. The continued presence of crania throughout Level 3 indicates that this behaviour was recurrent during this level's formation. This behaviour seems to have no subsistence-related purpose but to be more symbolic in its intent., (© 2023. The Author(s).)

Introduction: Basic life support training in school age is a topical issue because, with adequate training, any person can help save a life., Methods: Cluster clinical trial with data collection through an ad hoc self-administered, semi-structured questionnaire. The target population encompassed the students aged 4-6 years enrolled in 49 educational centres. The centres were randomly allocated to the intervention or control group. The intervention group was trained with the RCParvulari® methodology, consisting of theoretical and practical training on the first link of the chain of survival. The control group only received theoretical training. We evaluated participants before and immediately after the intervention and between 3 and 12 months post intervention by means of the questionnaire. We assessed the acquisition and retention over time of the knowledge and skills covered in the training compared to previous trainings in both groups., Results: A total of 1327 schoolchildren (79% of the target population) participated. The level of knowledge acquired immediately after training and after 3-12 months compared to baseline was significantly better (P < .001) in the intervention group than in the control group, both in early recognition and contacting of emergency services (112) and in remembering the "mouth-nose-eyes" mnemonic., Conclusions: The RCParvulari® methodology significantly contributed to an improved ability to recognize a possible medical emergency, start the chain of survival by alerting an adult and call the 112 emergency number in students in the last year of preschool education., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Patterned cell death is a common feature of many neurodegenerative diseases. In patients with autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and mouse models of ARSACS, it has been observed that Purkinje cells in anterior cerebellar vermis are vulnerable to degeneration while those in posterior vermis are resilient. Purkinje cells are known to express certain molecules in a highly stereotyped, patterned manner across the cerebellum. One patterned molecule is zebrin, which is expressed in distinctive stripes across the cerebellar cortex. The different zones delineated by the expression pattern of zebrin and other patterned molecules have been implicated in the patterning of Purkinje cell death, raising the question of whether they contribute to cell death in ARSACS. We found that zebrin patterning appears normal prior to disease onset in Sacs -/- mice, suggesting that zebrin-positive and -negative Purkinje cell zones develop normally. We next observed that zebrin-negative Purkinje cells in anterior lobule III were preferentially susceptible to cell death, while anterior zebrin-positive cells and posterior zebrin-negative and -positive cells remained resilient even at late disease stages. The patterning of Purkinje cell innervation to the target neurons in the cerebellar nuclei (CN) showed a similar pattern of loss: neurons in the anterior CN, where inputs are predominantly zebrin-negative, displayed a loss of Purkinje cell innervation. In contrast, neurons in the posterior CN, which is innervated by both zebrin-negative and -positive puncta, had normal innervation. These results suggest that the location and the molecular identity of Purkinje cells determine their susceptibility to cell death in ARSACS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Toscano Márquez, Cook, Rice, Smileski, Vieira-Lomasney, Charron, McKinney and Watt.)

Objectives: In this paper, we introduce the use of generalized linear mixed models (GLMM) as a better alternative to traditional statistical methods for studying factors associated to the prevalence of degenerative joint disease (DJD) in bioarchaeological contexts., Materials and Methods: DJD prevalence was assessed for the appendicular joints and the spine of a Spanish population dated from the 15th to the 18th century. Data were analyzed using contingency tables, logistic regression models, and logistic GLMM., Results: In general, results from GLMMs find agreement in other methods. However, by being able to analyze the data at the level of individual bones instead of aggregated joints or limbs, GLMMs are capable of revealing associations that are not evident in other frameworks., Discussion: Currently widely available in statistical analysis software, GLMMs can accommodate a wide array of data distributions, account for hierarchical correlations, and return estimates of DJD prevalence within individuals and skeletal locations that are unbiased by the effect of covariates. This gives clear advantages for the analysis of bioarchaeological datasets which can lead to more robust and comparable analyses across populations., (© 2020 Wiley Periodicals LLC.)

Acetylcholine acts as a neurotransmitter/neuromodulator of many central nervous system processes such as learning and memory, attention, motor control, and sensory processing. The present study describes the spatial distribution of cholinergic neurons throughout the brain of the weakly electric fish, Apteronotus leptorhynchus, using in situ hybridization of choline acetyltransferase mRNA. Distinct groups of cholinergic cells were observed in the telencephalon, diencephalon, mesencephalon, and hindbrain. These included cholinergic cell groups typically identified in other vertebrate brains, for example, motor neurons. Using both in vitro and ex vivo neuronal tracing methods, we identified two new cholinergic connections leading to novel hypotheses on their functional significance. Projections to the nucleus praeeminentialis (nP) arise from isthmic nuclei, possibly including the nucleus lateralis valvulae (nLV) and the isthmic nucleus (nI). The nP is a central component of all electrosensory feedback pathways to the electrosensory lateral line lobe (ELL). We have previously shown that some neurons in nP, TS, and tectum express muscarinic receptors. We hypothesize that, based on nLV/nI cell responses in other teleosts and isthmic connectivity in A. leptorhynchus, the isthmic connections to nP, TS, and tectum modulate responses to electrosensory and/or visual motion and, in particular, to looming/receding stimuli. In addition, we found that the octavolateral efferent (OE) nucleus is the likely source of cholinergic fibers innervating the ELL. In other teleosts, OE inhibits octavolateral hair cells during locomotion. In gymnotiform fish, OE may also act on the first central processing stage and, we hypothesize, implement corollary discharge modulation of electrosensory processing during locomotion., (© 2020 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

This work analyzes how the assumption of responsibility by aggressors convicted for gender-based violence is related to sexist attitudes, self-esteem and perceived functional social support. Similarly, the predictive capacity of these variables is studied with respect to the aggressors' minimization of the harm done and a lack of attributing responsibility to themselves. The participants in the research were males condemned to prison sentences for crimes related with gender-based violence in Spain. The instruments applied were the Attribution of Responsibility and Minimization of Harm Scale, the Ambivalent Sexism Inventory (ASI), the Rosenberg Self-Esteem Scale (RSE), the Functional Social Support Questionnaire (FSSQ), and the Social Desirability Scale (SDS). The study concludes that sexist attitudes are related with a greater lack of attribution of responsibility, as well as with a greater tendency to minimize the harm done by the aggression. In addition, the aggressors with low self-esteem use self-defense as a strategy to justify the violence. Similarly, the presence of an adequate social support network for the aggressor increases the attribution of responsibility on the part of those convicted for gender-based violence.

Introduction: Dysembryoplastic neuroepithelial tumours (DNET) are a type of benign glioneuronal neoplasia of typically temporal location that produce drug-resistant epileptic seizures in children and young adults., Objective: This work aims to assess the usefulness of functional magnetic resonance imaging (fMRI) in the preoperative study in four patients with DNET. A Philips Intera 3.0 Tesla magnetic resonance imaging scanner and the Blood-Oxygen-Level-Dependent (BOLD) technique were used to obtain the images, making it possible to locate the eloquent areas for language and motor areas through the application of specific paradigms., Results: In one case the tumour was adjacent to Broca's area, in two cases it coincided with Wernicke's area, in one patient it was<1cm from the motor area for the hand and in another close to memory. Only two of the patients were operated on, without postoperative functional deficit. Hemispheric activation contralateral to the tumour suggestive of neuroplasticity was observed in one of the patients., Conclusions: fMRI is a non-invasive method that allows us to assess the proximity of lesions to eloquent areas, which is key in the evaluation of surgical risk. In addition, it allowed the detection of probable neuroplasticity in one case, which guaranteed the success of the surgery., (Copyright © 2019 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

The olive oil assessment involves the use of a standardized sensory analysis according to the "panel test" method. However, there is an important interest to design novel strategies based on the use of Gas Chromatography (GC) coupled to mass spectrometry (MS), or ion mobility spectrometry (IMS) together with a chemometric data treatment for olive oil classification. It is an essential task in an attempt to get the most robust model over time and, both to avoid fraud in the price and to know whether it is suitable for consumption or not. The aim of this paper is to combine chemical techniques and Deep Learning approaches to automatically classify olive oil samples from two different harvests in their three corresponding classes: extra virgin olive oil (EVOO), virgin olive oil (VOO), and lampante olive oil (LOO). Our Deep Learning model is built with 701 samples, which were obtained from two olive oil campaigns (2014-2015 and 2015-2016). The data from the two harvests are built from the selection of specific olive oil markers from the whole spectral fingerprint obtained with GC-IMS method. In order to obtain the best results we have configured the parameters of our model according to the nature of the data. The results obtained show that a deep learning approach applied to data obtained from chemical instrumental techniques is a good method when classifying oil samples in their corresponding categories, with higher success rates than those obtained in previous works., (Copyright © 2020 Vega-Márquez, Nepomuceno-Chamorro, Jurado-Campos and Rubio-Escudero.)

Objective: The aims of our study were to evaluate tumour response in a series of patients with vestibular schwannoma (VS) treated with linear accelerator stereotactic radiosurgery (LINAC-RS), to describe the complications and to analyze the variables associated with the response to treatment., Material and Methods: This retrospective descriptive study included 64 patients treated from 2010 to 2016 with a minimum follow-up of one year, excluding patients with neurofibromatosis. Clinical-radiological parameters were evaluated. The treatment was performed using LINAC-RS. The prescribed dose was 12Gy at 90% isodose., Results: The mean age at treatment was 53 years, 56% were women. Ninety-eight percent of the patients had hearing loss, 71% with grade III according to the Gardner-Robertson Classification. The mean volume at treatment was 2.92cc and the mean follow-up, 40.95 months. The overall therapeutic success was 90%, reaching 100% at 12 and 24 months, and 86% after 36 months of follow-up. The radiological result was significantly related to the initial tumour volume (p<0.037). In 20 patients there was evidence of transient tumour growth compatible with pseudoprogression. Acute complications were present in 37.5%, and transitory complications in 50%. Chronic complications were found in 20%, with 84% being permanent. The rate of acute complications was lower in patients with regression (p<0.016). Chronic complications were more frequent in the 41-60 year old age group (p<0.040)., Conclusions: In our study, the overall tumour control was in accordance with other published series. The radiological result significantly related to the tumour volume at the commencement of treatment. The rate of acute complications was lower in patients with regression., (Copyright © 2019 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

In this paper, we report on the enhanced control of resistive switching in multilayer Si/SiO 2 structures, which permit the formation of Si nanocrystals with a typical size of 5.88 nm and overall good shape homogeneity. The deposition of a different number of Si and SiO 2 bilayers (6, 8 and 10) allowed control of SET/RESET voltages in negative bias ranges 4.5-10 V and 6.3-13 V for six- and ten-bilayer devices, respectively. The corresponding resistance ratio between ON/OFF states varied in the ranges 10 7 -10 5 for the aforementioned number of bilayers. Based on the result of XPS measurements, we suggest that the resistive switching in the studied system occurs due to the formation and annihilation of Si-Si and Si-O bonds, which serve as conductive pathways and isolating material, respectively.

Key Points: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative human disease characterized in part by ataxia and Purkinje cell loss in anterior cerebellar lobules. A knock-out mouse model has been developed that recapitulates several features of ARSACS. Using this ARSACS mouse model, we report changes in synaptic input and intrinsic firing in cerebellar Purkinje cells, as well as in their synaptic output in the deep cerebellar nuclei. Changes in firing are observed in anterior lobules that later exhibit Purkinje cell death, but not in posterior lobules that do not. Our results show that both synaptic and intrinsic alterations in Purkinje cell properties likely contribute to disease manifestation in ARSACS; these findings resemble pathophysiological changes reported in several other ataxias., Abstract: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that includes a pronounced and progressive cerebellar dysfunction. ARSACS is caused by an autosomal recessive loss-of-function mutation in the Sacs gene that encodes the protein sacsin. To better understand the cerebellar pathophysiology in ARSACS, we studied synaptic and firing properties of Purkinje cells from a mouse model of ARSACS, Sacs -/- mice. We found that excitatory synaptic drive was reduced onto Sacs -/- Purkinje cells, and that Purkinje cell firing rate, but not regularity, was reduced at postnatal day (P)40, an age when ataxia symptoms were first reported. Firing rate deficits were limited to anterior lobules that later display Purkinje cell death, and were not observed in posterior lobules where Purkinje cells are not lost. Mild firing deficits were observed as early as P20, prior to the manifestation of motor deficits, suggesting that a critical level of cerebellar dysfunction is required for motor coordination to emerge. Finally, we observed a reduction in Purkinje cell innervation onto target neurons in the deep cerebellar nuclei (DCN) in Sacs -/- mice. Together, these findings suggest that multiple alterations in the cerebellar circuit including Purkinje cell input and output contribute to cerebellar-related disease onset in ARSACS., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

Aim/Materials & methods: Few studies have evaluated the influence of pharmacogenetics in psoriatic patients treated with ustekinumab. We evaluated 121 polymorphisms to study a possible association between these SNPs and the response to ustekinumab (PASI75 at 4 months; n = 69)., Results/conclusion: The adjusted results (false discovery rate) showed an association between five SNPs in TNFRSF1A, HTR2A, NFKBIA, ADAM33 and IL13 genes, and poor response to ustekinumab. Furthermore, six SNPs in CHUK, C17orf51, ZNF816A, STAT4, SLC22A4 and Corf72 genes were associated with better response to ustekinumab. However, there was no significant association between response to ustekinumab and SNPs in HLA-C as it has been recently described. Finally, a higher weight was obtained in nonresponders than responders (p = 0.018). Further studies would be necessary to be closer to personalized medicine.

Several interleukin 6 gene (IL6) polymorphisms are implicated in susceptibility to rheumatoid arthritis (RA). It has not yet been established with certainty if these polymorphisms are associated with the severe radiographic damage observed in some RA patients, particularly those with the development of joint bone ankylosis (JBA). The objective of the present study was to evaluate the association between severe radiographic damage in hands and the -174G/C and -572G/C IL6 polymorphisms in Mexican Mestizo people with RA. Mestizo adults with RA and long disease duration (>5 years) were classified into two groups according to the radiographic damage in their hands: a) severe radiographic damage (JBA and/or joint bone subluxations) and b) mild or moderate radiographic damage. We compared the differences in genotype and allele frequencies of -174G/C and -572G/C IL6 polymorphisms (genotyped using polymerase chain reaction-restriction fragment length polymorphism) between these two groups. Our findings indicated that the -174G/C polymorphism of IL6 is associated with severe joint radiographic damage [maximum likelihood odds ratios (MLE&#95;OR): 8.03; 95%CI 1.22-187.06; P = 0.03], whereas the -572G/C polymorphism of IL6 exhibited no such association (MLE&#95;OR: 1.5; 95%CI 0.52-4.5; P = 0.44). Higher anti-cyclic citrullinated peptide antibody levels were associated with more severe joint radiographic damage (P = 0.04). We conclude that there is a relevant association between the -174G/C IL6 polymorphism and severe radiographic damage. Future studies in other populations are required to confirm our findings.

The extracellular matrix (ECM) influences different physiological and pathophysiological aspects of the cell. The ECM consists in a complex network of macromolecules with characteristic biochemical properties that allow cells to sense their environments inducing different signals and changing cell behavior. The purpose of the present study was to evaluate the participation of different ECM proteins in cell morphology and its implication on motility, proliferation and hormone secretion in GH3 cells, a tumor pituitary cell. GH3 cells were cultured with a defined medium on collagens I/III and IV, fibronectin and laminin. GH3 cells express α2 integrin subunit de novo. The cells responded to the ECM proteins with differentiated cell surface morphologies and membrane protrusions. A rounded shape with small membrane blebs, weak substrate adhesion and high motility was observed in cells on C I/III and fibronectin, while on C IV and laminin cells were viewed elongated and adhered. Differences on actin cytoskeleton, cytoskeletal-associated vinculin and phospho-MLC showed that ECM proteins determine the cytoskeleton organization. Cell proliferation showed dependency on the ECM protein, observing a higher rate in cells on collagen I/III. Prolactin secretion was higher in cells with small blebs, but an unchangeable response to EGF was obtained with the ECM proteins, suggesting is a consequence of cortical actin arrangement. We ascribe the functional differences of the GH3 cells to the cytoskeletal organization. Overall, the data showed that ECM plays a critical role in GH3 cells modulating different cellular comportment and evidenced the importance of the ECM composition of pituitary adenomas.

Various neuromodulators have been shown to be involved in shaping the sensory information available to the brain. Acetylcholine (ACh) modulation, through muscarinic receptors, is a particularly widespread mechanism of controlling sensory information transmission. The precise effects of ACh modulation depend on the subtype of muscarinic ACh receptors that are activated. In weakly electric fish, previous work suggested a role of ACh, via muscarinic receptors, in the modulation of information transmission in the electrosensory lateral line lobe (ELL) of the hindbrain. In this study, we determined which muscarinic receptor (mAChR) subtypes are present in the brain of Apteronotus leptorhynchus as well as their spatial distribution. We partially cloned three subtypes of muscarinic receptors (mAChR2, -3, and -4) from brain tissue of A. leptorhynchus and used in situ hybridization in transverse sections of the brain to determine their distributions. Sites labeled for the three muscarinic receptor mRNAs were found in various brain regions devoted to the processing of different sensory modalities. The mRNA probes for the three receptor types showed differential distribution but also overlapping presence of two or more receptors in particular nuclei. In addition to the presence of mAChR3 in the ELL region, electrosensory nuclei including the nucleus praeeminentialis, dorsal torus semicircularis and optic tectum showed expression of one or more mAChRs. Thus, the overall pattern of mAChR expression found is in agreement with mAChR expression in other species, with additional presence evident in specialized regions of the electrosensory system, which suggests an important modulating role of ACh in this sensory modality., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: The ACTN3 gene encodes the fast muscle protein α-actinin-3. The ACTN3 R577X polymorphism is a premature stop codon and results in absence of α-actinin-3 in 577XX homozygotes. The aim of this study was to determine the ACTN3 genotype in idiopathic inflammatory myopathies (IIMs)., Methods: We performed ACTN3 genotyping on 27 patients with dermatomyositis (DM), 10 with polymyositis (PM), and 85 healthy subjects. Muscle enzyme levels of creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were recorded at the time of diagnosis and recruitment. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the allele frequency was analysed., Results: A total of 36% of healthy subjects had the ACTN3 577XX polymorphism (α-actinin-3 deficiency), 18% had the 577RR (homozygous wild type) genotype, and 46% 577RX (heterozygous). In DM/PM, 70% had the ACTN3 577XX polymorphism, 6% RR, and 24% RX [odds ratio (OR) 4.12, 95% confidence interval (CI) 1.67-10.33, p < 0.001]. In healthy subjects, the R allele was present in 41% and the X allele in 59% compared to 18% and 82%, respectively, in the IIM group (OR 3.21, 95% CI 1.57-6.66, p < 0.001). Thus, the ACTN3 577X allele seemed to increase the risk of developing IIM, and DM in particular, although this was not related to severity of expression of the phenotype., Conclusions: The ACTN3 577X allele appeared to increase the risk of developing IIM; 70% of IIM patients were deficient in α-actinin-3. By contrast, ACTN3 577XX patients seemed to have less severe disease as reflected in lower muscle enzyme levels.

Background: The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing., Methodology/principal Findings: We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU(+)) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU(+) nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU(+)/CldU(+)). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU(+)/CldU(+) cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34(+) and BrdU-retaining cells of the hair follicles., Conclusions/significance: Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation may play a functional role in the modulation of hair SC physiology during wound healing.

Innervation is required to preserve several aspects of skin homeostasis. Previous studies in rodents have shown that sciatic nerve transection leads to epidermal thinning and reduced keratinocyte proliferation. As the sciatic nerve is composed of sensory and motor axons, it is not clear whether skin alterations reflect motor or sensory disturbances. In this study, we used neonatal capsaicin treatment to evaluate whether sensory chemical denervation affects keratinocyte proliferation at 1, 3, and 6 months of age. Using design-based stereological methods, we estimated the total length of intraepidermal nerve fibers (IENF) that were of peptidergic type and the number of bromodeoxyuridine-labeled (BrdU(+) ) nuclei in the hind paw glabrous epidermis of control and capsaicin-treated rats. We found that the treatment decreased the total fiber length of IENF immunoreactive for both protein gene product 9.5 (PGP(+) ) and of IENF immunoreactive for calcitonin gene-related peptide (CGRP(+) ). The length of PGP(+) fibers decreased by 83%, 81%, and 77% and that of CGRP(+) fibers decreased by 48%, 58%, and 58% at 1, 3, and 6 months, respectively. Double-immunofluorescence staining for neural beta III tubulin and CGRP revealed that the majority of the remaining fibers in the epidermis after capsaicin treatment were of peptidergic type. The number of BrdU(+) nuclei was similar in both groups. Our findings suggest that IENF present after capsaicin treatment are sufficient to maintain epidermal replacement., (2010 Wiley-Liss, Inc.)

Objectives: Chronic liver diseases caused by hepatitis B (HBV) or C virus (HCV) are common worldwide. Despite reports on autoimmunity in viral hepatitis, studies on autoantibodies associated with systemic rheumatic diseases are inconsistent. Testing of a small number of selected autoantibody specificities using ELISA appears to be one reason for inconsistency. Sera from patients with viral hepatitis were tested by immunoprecipitation that will allow unbiased screening of autoantibodies found in systemic rheumatic diseases., Methods: Ninety Mexican patients (37 male, 53 female, 26 HBV, 6 HBV+HCV, 58 HCV) with chronic viral hepatitis, confirmed by nested or RT-nested-PCR, HBsAg and anti-HCV antibodies, were studied. Autoantibodies were tested by immunofluorescence, immunoprecipitation and ELISA. Specificities were verified using reference sera., Results: Antinuclear antibodies were found in 38% HBV, 17% HBV+HCV, and 28% in HCV. Autoantibodies to Argonaute (Ago2, Su antigen), a microRNA binding protein that plays a key role in RNA-induced silencing complex (RISC), was found in 5% (4/64) of HCV or HBV+HCV coinfected patients but not in HBV (0/26). Anti-Ago2/Su was found in 1/2 of I-IFN-treated case vs. 3/62 in cases without I-IFN. HCV did not have other lupus autoantibodies whereas 19% (5/26) of HBV had anti-U1RNP+Ku, Ro+La, RNA polymerase II, or possible U5snRNPs., Conclusions: Lupus autoantibodies were uncommon in HCV except anti-Ago2/Su. HCV and I-IFN have many ways to affect TLR signaling, miRNA and miRNA binding protein Ago2/Su. To understand the mechanism of specific targeting of Ago2 in HCV may provide a clue to understand the mechanism of specific autoantibody production.

Blindness leads to a major reorganization of neural pathways associated with touch. Because incoming somatosensory information influences motor output, it is plausible that motor plasticity occurs in the blind. In this work, we evaluated this issue at the peripheral level in enucleated rats. Whisker muscles in enucleated rats 160 days of age or older showed increased cytochrome oxidase activity, capillary density, motor plate size, and amplitude of evoked field potentials as compared with their control counterparts. Such differences were not observed at ages 10 and 60 days, the capillary density was the exception being greater in the enucleated rat at the latter age. Interestingly, there was a trend to increased neurotrophin-3 concentrations in the whisker pads of enucleated rats throughout postnatal development. Our results show that neonatal enucleation leads to late onset plasticity of the whisker's motor system.